不可逆蛋白激酶抑制剂研究进展

Advances in Irreversible Protein Kinase Inhibitors

蛋白激酶是一个由多种高度保守酶组成的酶系,主要负责将ATP的γ-磷酸基团转移给酪氨酸、丝氨酸、苏氨酸等多种氨基酸,这些氨基酸在细胞中起到信号传导的作用。迄今为止,多数上市的激酶抑制剂是ATP竞争的非共价抑制剂,但是近来不可逆蛋白抑制因其可以和半胱氨酸或其他亲核残基在ATP口袋处结合形成共价键而备受科研人员的青睐。通过讲述不可逆蛋白激酶抑制剂的研究进展,探讨新型共价抑制剂的高效发展战略。

Protein kinases are a highly conserved enzyme systerm by a variety of enzymes,which are primarily responsible for the transfer of ATP γ-phosphate groups to tyrosine,serine,threonine and other amino acids. These amino acids play a role in signal transduction in cells. To date,the majority of listed kinase inhibitors are non-covalent ATP competitive inhibitors.But recently, the development of an irreversible inhibitors is favored by researchers, because of they can combine with cysteine or other nucleophilic amino acids residues to form covalent bonds in the ATP binding pocket. This article is mainly about the research progress in irreversible protein kinase inhibitors,and discussed the efficient development strategies of new covalent inhibitors.